There are many known and successful techniques for providing taste masked dosage forms including taste masked orally disintegrable and/or dissolvable dosage forms (“ODT”). These techniques include a number which are owned by the assignee, CIMA LABS INC., 10000 Valley View Rd, Eden Prairie Minn., such as U.S. Pat. Nos. 5,178,878 and 5,223,264, which describe taste masked ODTs produced using, inter alia, a protected particle and effervescents. See also U.S. Pat. Nos. 5,503,846, 5,607,697, and 6,024,981.
Another generally successful technique is described in CIMA's U.S. Pat. No. 6,740,341. That patent describes a dual coating system used for particularly objectionable drugs which included a spacing layer overcoating a granulate, followed by the application of an overcoating layer of a taste masking material. The spacing layer helps prevent puncture or compromise of the taste masking layer particularly by sharp or jagged crystalline materials. The examples describe a spacing layer composed of 20% by weight gain or more of ethyl cellulose and PVP or ethyl cellulose and HPMC. See also Kais et al., U.S. Pat. No. 5,516,524.
While CIMA's techniques have been highly successful in a technical sense, there are nonetheless situations and drugs where further development is necessary to obtain adequate performance in terms of construction, taste masking performance and drug delivery. One such particularly challenging drug is prednisolone. The sodium phosphate salt (a term which includes any sodium and phosphate containing salt such as, without limitation, prednisolone disodium phosphate, unless otherwise indicated.) of this drug is known to be used to treat a vast array of conditions including: allergic states, dermatologic diseases, endocrine disorders, neoplastic disorders, and rheumatic disorders and the acetate salt is known for use in ophthalmic preparations. Products are also currently available using the free base material in a traditional swallow tablet or in a liquid.
While the free base form of prednisolone is objectionable tasting, it is not so objectionable that its taste cannot be managed by fairly routine techniques. However, it does present solubility and bioavailability problems. Prednisolone sodium phosphate has good solubility and bioavailability. But its taste is abysmal—far more than many taste masking strategies can handle. Indeed, it is believed that, in no small measure because of its aggressively objectionable flavor, prednisolone salts and, in particular, the sodium phosphate salt, are not only not available as ODT tablets, they are not available as tablets at all. The only dosage form that is available for this particular drug salt is a liquid where its objectionable flavor can be diluted—indeed drowned—by conventional sweeteners, flavorings and other masking techniques.
The sheer volume of the materials required to provide adequate taste masking in a liquid would suggest to formulators that any tablet formulation, let alone an ODT which is intended to dissolve/disintegrate in the mouth, is unattainable. While the volume of liquid that constitutes a dose can vary widely, tablets can only be so big. Too large a tablet or too many tablets would not be accepted in the marketplace. Tablets of greater than about 1 gram are rare and pose significant problems to many who are squeamish about swallowing, including children and the elderly. Thus, the multiple demands made of tablets in terms of excipients, the amount of active, processability, and size significantly limit the availability and room for many traditional taste masking strategies in solid tablets. And with a material as bad tasting as this, it is no wonder only a liquid form exists.